The formation of aromatic carboxylic acids having a heteroatom containing substituent remains a complicated process. The reaction conditions needed to generate a carboxylate moiety are characterized by at least one problem of inducing undesired reaction of heteroatom substituted groups, mixed isomer formation, or resort to organometallic or heavy metal catalysts. As a result many substituted aromatic carboxylic acids produce waste streams of undesirable isomers and heavy metal waste.
By way of example, for the preparation of dinitrobenzoic acids, 2,6-dinitrobenzoic acid (2,6-DNBA) has been prepared by oxidation of 2,6-dinitrotoluene with acidic dichromate in moderate 58% yield (Austr. J. Chem. 1980, 33, 2777-2779). However, the use of chromium-containing oxidizing agent involves disposal of chromium-containing waste which is costly due to its toxicity. The use of less toxic but more expensive potassium permanganate produces 2,6-DNBA only in low yield (19%) (Chemosphere, 1999, 38, 3119-3130). 2,6-dinitrotoluene, which is described in these publications as a starting material, can be synthesized by direct nitration of toluene. However, the nitration results in mixtures of dinitrotoluene isomers, of which 2,6-dinitrotoluene is only a minor component, reducing significantly the overall yield of the target molecule. Deady et al. prepared 2,6-DNBA from 2,6-dinitrobenzyl bromide which was first oxidized to 2,6-dinitrobenzaldehyde in 40% yield using mercury(I) nitrate. The aldehyde obtained was then oxidized to 2,6-DNBA with aqueous permanganate in 65% yield (Org. Prep. Proc. Int. 2003, 65, 627-630). 2,6-dinitrobenzyl bromide used as the starting material was prepared from 2,6-dinitrotoluene by free radical bromination. Accordingly, the synthesis is rather complicated, and the use of highly toxic mercurates is needed. Buck et al. treated 2,6-dinitrobromobenzene with PhLi followed by carbonation to afford the target 2,6-DNBA in a reported 67% yield (Angew. Chem. Int. Ed. Engl., 1966, 5, 1044). However, 2,6-dinitrobromobenzene used as the starting material has to be prepared from benzene via multistep low yielding approaches. Kosuge et al. have reported that 5-nitroquinoline can be oxidized to 2,6-DNBA with hydrogen peroxide in acetic acid in 23% yield (Pharm. Bull. 1954, 2, 397-400). Since the resinous substances formed made the isolation of 2,6-DNBA difficult, a further permanganate oxidation was needed to decompose the contaminants.
Other aromatic carboxylic acids containing heteroatom containing substituents that include amine or hydroxyl substituent of phenyl or conjugated aromatic ring systems also suffer these problems in synthetic preparation. Thus, there exists a need for a method to produce aromatic carboxylic acids having a heteroatom containing substituent operative at high yield.